PHGPX AND PHOSPHOLIPASE A(2) GPX - COMPARATIVE IMPORTANCE ON THE REDUCTION OF HYDROPEROXIDES IN RAT-LIVER MITOCHONDRIA/

The comparative importance of phospholipid hydroperoxide glutathione p eroxidase (PHGPx) and of ''classic'' glutathione peroxidase (GPx) in t he reduction of phospholipid hydroperoxides is unclear. Although GPx a ctivity is 500-fold higher than that of PHGPx in rat liver,(1) the red uction of phospholipid hydroperoxides by glutathione (GSH) through GPx may be strongly limited by a low PLA2 activity. We address this issue using a moderately detailed kinetic model of mitochondrial lipid pero xidation in rat liver. The model was based on published data and was s ubjected to validation as reported in the references.' It is analysed by computer simulation and sensitivity analysis. Results suggest that in rat liver mitochondria PHGPx is responsible for almost all phosphol ipid hydroperoxide reduction. Under physiological conditions, the esti mated flux of phospholipid hydroperoxides reduction through PHGPx is a bout four orders of magnitude higher than the estimated hydrolysis Aux through PLA2. On the other hand, virtually all hydrogen peroxide is r educed through GPx. Therefore, a functional complementarity between PH GPx and GPx is suggested. Because the results are qualitatively robust to changes of several orders of magnitude in PLA2 and PHGPx levels, t he conclusions may not be limited to mitochondria.